Optimisation of Functional Magnetic Resonance Imaging Protocols for Investigation of Subregional Amygdala Functional Connectivity in Major Depressive Disorder

Abstract

Amygdala dysfunction is strongly implicated in emotion dysregulation across multiple psychiatric conditions and represents a key mechanism underlying symptoms of Major Depressive Disorder (MDD). Functional Magnetic Resonance Imaging (fMRI) at 3 Tesla (3T) has been extensively used to investigate the neural underpinnings of the amygdala, a small structure that has traditionally been considered as a single entity in data analysis. However, its composition of nine structurally and functionally heterogeneous subnuclei that form three main subregions make this approach challenging in the context of spatial specificity and accuracy of findings.

The overarching results of this work highlighted several compelling findings, notably that optimised 2D data acquisitions at 3T can achieve sufficient levels of spatial resolution to identify alterations in FC at a subregional rather than whole amygdala level, allowing differentiation of treatment resistant and treatment responsive depression cohorts as well as closely mirroring network FC findings reported at 7T. The work also showed that FC results are less sensitive when the amygdala is considered as a single structure rather than three individual subregions, and that newer techniques have the potential to reveal FC information in subcortical regions that are technically challenging to image well.

In the setting of limited access to higher spatial resolution imaging afforded by 7T systems, these results not only shine a spotlight on the underutilised capability of currently available MRI hardware, acquisition and analysis techniques, but taken together, the thesis findings illustrate that current fMRI protocols on 3T MRI systems can be optimised effectively to achieve more granular interrogation of amygdala function. This work highlights a feasible path forward, leading to an enhanced understanding of subregional amygdala dysfunction in MDD and other psychiatric conditions.